- 作者: Gang Wu; Changlong Nan;, Johnathon C Rollo; Xupei Huang; Jie Tian
- 作者服務機構: Department of Cardiology, the Children's Hospital of Chongqing Medical University, Chongqing, China
- 中文摘要: --
- 英文摘要:
Background: Valproic acid, a widely used anticonvulsant drug, is a potent teratogen
resulting in various congenital abnormalities. However, the mechanisms underlying valproic
acid induced teratogenesis are nor clear. Recent studies indicate that histone deacetylase is a
direct target of valproic acid.
Methods: In the present study, we have used histological analysis and RT-PCR assays to
examine the cardiac abnormalities in mice treated with sodium valproate (NaVP) and
determined the effects of NaVP on histone deacetylase activity and the expression of heart
development-related genes in mouse myocardial cells.
Results: The experimental data show that NaVP can induce cardiac abnormalities in fetal
mice in a dose-dependent manner. NaVP causes a dose-dependent inhibition of hitone
deacetylase (HDAC) activity in mouse myocardial cells. However, the expression levels of
HDAC (both HDAC1 and HDAC2) are not significantly changed in fetal mouse hearts after
administration of NaVP in pregnant mice. The transcriptional levels of other heart
development-related genes, such as CHF1, Tbx5 and MEF2, are significantly increased in
fetal mouse hearts treated with NaVP.
Conclusions: The study indicates that administration of NaVP in pregnant mice can result in
various cardiac abnormalities in fetal hearts, which is associated with an inhibition of histone
deacetylase without altering the transcription of this enzyme. - 中文關鍵字: --
- 英文關鍵字: --